key: cord-0006839-7rsmbk3j
authors: Coppola, M.; Porto, A.; De Santo, D.; De Fronzo, S.; Grassi, R.; Rotondo, A.
title: Influenza A virus: radiological and clinical findings of patients hospitalised for pandemic H1N1 influenza
date: 2011-01-12
journal: Radiol Med
DOI: 10.1007/s11547-011-0622-0
sha: 135434ccc207696d52d47ec6bd853361080db2ce
doc_id: 6839
cord_uid: 7rsmbk3j

PURPOSE: This paper describes the radiological and clinical findings identified in a group of patients with H1N1 influenza. MATERIALS AND METHODS: Between May and mid-November 2009, 3,649 patients with suspected H1N1 influenza presented to our hospital. Our study population comprised 167 (91 male, 76 female patients, age range 11 months to 82 years; mean age 29 years) out of 1,896 patients with throat swab positive for H1N1 and clinical and laboratory findings indicative of viral influenza. All 167 patients were studied by chest X-ray (CXR), and 20 patients with positive CXR and worsening clinical condition also underwent computed tomography (CT). The following findings were evaluated on both modalities: interstitial reticulation (IR), nodules (N), ground-glass opacities (GGO), consolidations (CONS), bacterial superinfection and pulmonary complications. RESULTS: Ninety of 167 patients had positive CXR results. Abnormalities identified on CXR, variously combined and distributed, were as follows: 53 IR, 5 N, 13 GGO, 50 CONS; the predominant combination was represented by six GGO with CONS. Of the 20 CXR-positive cases also studied by CT, 17 showed pathological findings. The abnormalities identified on CT, variously combined and distributed, were as follows: 14 IR, 2 N, 5 GGO; the predominant combination was 10 GGO with CONS. Despite the differences between the two modalities, the principle radiological findings of bacterial superinfection were tree-in-bud pattern, consolidation with air bronchogram, and pleural and pericardial effusion. Fifteen of the 20 patients studied by both CXR and chest CT showed respiratory complications with bilateral and diffuse CONS on CXR and CT. Six of 15 died: 4/6 of acute respiratory distress syndrome and 2/6 of multiple organ failure. CONCLUSIONS: Our study describes the radiological and clinical characteristics of a large population of patients affected by H1N1 influenza. CXR and chest CT identified the site and extent of the pulmonary lesions and documented signs of bacterial superinfection and pulmonary complications.

broncogramma aereo, versamento pleurico e pericardico. Dei 20 pazienti studiati con Rx e TC, 15 hanno presentato complicanze respiratorie con un quadro Rx e TC di OGG e CM diffusi e bilaterali. Sei/15 sono deceduti: 4/6 per acute respiratory distress syndrome (ARDS), 2/6 per multiple organ failure (MOF) . Conclusioni. Il nostro studio ha delineato le caratteristiche radiologiche e cliniche di un'ampia popolazione di pazienti con infl uenza H1N1. La Rx e la TC del torace hanno identifi cato sede ed estensione delle lesioni polmonari, documentando i segni di sovrainfezione batterica e le complicanze polmonari. [1, 2] . Il virus infl uenzale H1N1 è un sottotipo di Infl uenzavirus A appartenente alla famiglia delle Orthomyxoviridae, di cui sono note numerose varianti che, negli animali, causano forme infl uenzali pandemiche, come l'infl uenza aviaria e la febbre suina. Analisi genetiche suggeriscono che la comparsa della nuova linea H1N1 dell'infl uenza suina nell'uomo sia diretta conseguenza di un riassortimento dei genomi virali dell'infl uenza suina, aviaria ed umana del Nord America e dell'Eurasia [3] [4] [5] [6] . Nel mese di giugno 2009, in seguito alla documentazione pubblicata da parte della Organizzazione Mondiale della Sanità (OMS) del primo contagio interumano in due stati e alla rapida diffusione del virus, è stato dichiarato lo stato di emergenza mondiale di scala 6 (pandemia infl uenzale) [6, 7] . Febbre elevata, faringodinia, tosse, astenia, artromialgie, nausea, vomito e/o diarrea hanno costituito i principali sintomi d'esordio clinico dell'infl uenza H1N1; nei casi più complessi è insorta insuffi cienza respiratoria acuta [1, 6, 8] . Le principali alterazioni del quadro ematochimico sono state leucopenia, trombocitopenia, aumento degli indici di funzionalità epatica [1, 6, 8] . Il peculiare tropismo virale per l'apparato respiratorio ha determinato il ricorso alle tecniche di imaging per meglio caratterizzare sede, distribuzione e tipologia delle lesioni elementari polmonari [9] . L'esame radiografi co del torace (Rx) e la tomografi a computerizzata (TC) del torace hanno rappresentato le indagini bronchogram, and pleural and pericardial effusion. Fifteen of the 20 patients studied by both CXR and chest CT showed respiratory complications with bilateral and diffuse CONS on CXR and CT. Six of 15 died: 4/6 of acute respiratory distress syndrome and 2/6 of multiple organ failure. Conclusions. Our study describes the radiological and clinical characteristics of a large population of patients affected by H1N1 infl uenza. CXR and chest CT identifi ed the site and extent of the pulmonary lesions and documented signs of bacterial superinfection and pulmonary complications.

Keywords Infl uenza A virus · H1N1 subtype · Computed tomography · X-ray · Pneumonia · Viral

Swine-origin infl uenza -or swine infl uenza; swine fl u -is an acute respiratory infection caused by the novel infl uenza A, subtype H1N1, which was transmitted to humans from pigs in Mexico and the United States in March and April 2009 and rapidly spread worldwide [1, 2] . H1N1 virus is a subtype of the infl uenza A virus that belongs to the Orthomyxoviridae family, of which numerous variants exist that cause fl u pandemics among animals, such as bird fl u and swine fl u. Genetic analyses suggest that the emergence of the novel H1N1 strain of swine fl u in humans is the direct consequence of a reassortment of the viral genomes of swine fl u, bird fl u and human fl u in North America and Eurasia [3] [4] [5] [6] . In June 2009, following the report of the fi rst human-to-human transmission in two countries in one World Health Organization (WHO) region and the rapid spread of the virus, the WHO declared a level-6 pandemic alert [6, 7] . High fever, sore throat, cough, fatigue, joint pain, nausea, vomiting and/or diarrhoea are the principal symptoms of H1N1 infl uenza; more complex cases present with respiratory failure [1, 6, 8] . The main abnormalities in blood chemistry are leucopenia, thrombocytopenia and elevated liver function tests [1, 6, 8] . The specifi c tropism of the virus for the respiratory tract has led to the use of imaging to better characterise the location, distribution and type of the primary pulmonary lesions [9] . Chest X-ray (CXR) and chest computed tomography (CT) have been the investigations of choice for identifying and quantifying, respectively, pulmonary damage in patients affected by infl uenza A [10] [11] [12] . The aim of this paper is to describe the radiological and clinical fi ndings in patients hospitalised for a diagnosis of suspected H1N1 swine-origin infl uenza.

di riferimento ai fi ni rispettivamente dell'individuazione e quantifi cazione del danno polmonare nei pazienti affetti da infl uenza virale A [10] [11] [12] . Scopo del nostro studio è defi nire il quadro radiologico e clinico dei pazienti ospedalizzati per diagnosi di infl uenza virale H1N1 di origine suina. CXR was performed on all 167 patients, 20 of whom (11.9%) were also studied by CT to assess equivocal fi ndings on CXR or discrepancies between the CXR and clinical fi ndings. CXR was performed using the standard technique (posteroanterior projection: 10 mAs, 70 kV; lateral projection: 60 mAs, 80 kV; fi lm-focus distance 180 cm) with the patient in standing position in 150 cases (89.9%); only 17 patients (10.1%) were imaged in a sitting or lying position and with anteroposterior projection due to an inability to maintain a standing position and/or inspiration.

CT study was performed with a 64-detector-row CT scanner immediately after the CXR in 11/20 cases and 24 h after CXR in the remaining 9/20 cases. On clinical request, 18/20 patients -12/20 large and 6/20 poorly cooperative patients -underwent unenhanced chest and abdominal CT with the spiral technique: breath-hold volumetric scans, slice thickness 1 mm, kV 120, mA 180, pitch 1. Only 2/18 patients with suspected pulmonary embolism were subsequently imaged after intravenous administration of nonionic iodinated contrast material with the Sure Start technique at a fl ow rate of 3 ml/s and dose of 100 ml. The resulting CT images were viewed with a lung window (width 1,500 HU, level -700 HU) and mediastinal window (width 350 HU, level 40 HU). The remaining 2/20 patients were studied with high-resolution CT of the chest for clinical suspicion of concurrent interstitial pulmonary disease using a standard protocol: collimation 1 mm, interval 10 mm, acquisition time 1-2 s, high-spatial-frequency reconstruction algorithm, matrix 512 × 512, 120 kV, 200 mA, FOV encompassing both lungs, window level -600 HU (range -500/-900 HU), window width 1,500 HU (range 1,100/2,000 HU), expiratory scans and patient in prone position when needed. Two radiologists independently examined and interpreted the CXR and CT images stored in the Picture Archiving and Communications System (PACS).

The primary lesions assessed at CXR and chest CT were [13] and recent publications [10, 11] describing the main radiological pulmonary manifestations of A/H1N1 infl uenza: interstitial reticulation (RI; linear opacities of the central and peripheral interstitium appearing as radio-opaque lines on CXR and hyperdensities on CT), nodules (N; well-or illdefi ned, rounded opacities/hyperdensities, with maximum diameter of 3 cm.), ground-glass opacities (GGO; heterogeneous increase in parenchymal opacity with preservation of bronchial and vascular margins), consolidation (CONS; homogenously increased parenchymal attenuation that obscures the margins of the bronchial and vessels walls).

Images were also assessed for signs of bacterial suprainfection: consolidation with air bronchogram (area of radiolucency at CXR and low attenuation at CT, refl ecting the air-fi lled bronchi on a background of opaque or high-attenuation airless lung), cavitations (gas-fi lled spaces, seen as lucencies or low-attenuation areas within a parenchymal consolidation), tree-in-bud pattern (branching centrilobular structures), pleural and/or pericardial effusion (fl uid in the pleural/pericardial cavity), lymphadenopathy (short-axis diameter >1 cm for mediastinal nodes and >3 mm for hilar nodes). In patients with suspected bacterial suprainfection, blood and bronchoaspirate cultures were ordered to search for pathogenic microorganisms. Lastly, the images were assessed for possible pulmonary complications. Extent of pulmonary damage was defi ned univocally at CXR and chest CT: unilateral or bilateral; symmetrical or asymmetrical; focal, multifocal or diffuse; with predominant distribution in the upper, middle or lower lobes. On CT we also determined the predominant distribution of lesions as being central (perihilar) or peripheral (subpleural). Multiplanar reconstructions (MPR) and maximum intensity projections (MIP) were obtained through postprocessing in all patients studied with volumetric CT scans. Table 2) : IR was seen in 14 (82.3%), N in 2 (11.7%), GGO in 5 (29.4%). The predominant combination was GGO with CONS, seen in 10 (58.8%). None of the patients showed isolated pulmonary consolidation, and none of those studied with contrast-enhanced multidetector-row CT (MDCT) showed direct and/or indirect signs of pulmonary embolism.

On CXR, fi ndings suggestive of bacterial suprainfection were seen in various combinations in 14/90 patients (15.5%) ( Table 1) : pleural effusion in 9/14 (64.2%), consolidation with air bronchogram in 4 (28.5%), lymphadenopathy in 2 (14.2%), cavitation in 1 (7.1%), hydropneumothorax in 1 (Table 2) : tree-in-bud pattern in 9/9 (100%), consolidation with air bronchogram in 6 (66.6%), pleural effusion in 4 (44.4%) and pericardial effusion in 3 (33.3%), lymphadenopathy >1 cm in 2 (22.2%), cavitation in 1 (11.1%), and hydropneumothorax in 1 (11.1%). CT confi rmed the CXR fi ndings of bacterial suprainfection in 9 cases (9/14, 64.2%) and identifi ed as false positive fi ve cases of suspected pleural effusion detected on CXR. In all fi ve cases, the radiograms had been obtained in the supine position and with anteroposterior projection only in poorly cooperative patients. In addition, in 2/9 cases in which CT confi rmed CXR signs of bacterial suprainfection, it also revealed consolidations with air bron- chogram, which had gone undetected on CXR. These were located in the basal and retrocardiac regions in radiograms acquired with anteroposterior projection only. Finally, in 3/9 patients in whom CT confi rmed the CXR signs of bacterial suprainfection, it also identifi ed the presence of pericardial effusion, which had been missed at CXR in all cases owing to very small size.

Blood and bronchoaspirate culture identifi ed Staphylococcus aureus in 3/9 patients and a mixed bacterial fl ora in 6/9 cases. In 15/167 patients (8.98%), worsening clinical and radiological features required orotracheal intubation and mechanical ventilation after admission to the Intensive Care Unit. All of these patients were affected by an underlying condition: arterial hypertension complicated by placenta previa and postpartum uterine atony (1/15; 6.6%), hypertensive cardiopathy (3/15; 20%), emphysema (3/15; 20%), bullous dystrophy (1/15; 6.6%), rib-cage malformations (2/15; 13.3%), obesity (4/15; 26.6%), diabetes (2/15; 13.3%), and drug abuse (1/15; 6.6%). In all cases, CXR and CT fi ndings were characterised by bilateral and diffuse GGO with CONS (Figs. 3a, b, 4a-c) . Death occurred in 6/15 (40%) patients due to acute respiratory distress syndrome (ARDS) in four cases and multiple organ failure in two.

Human infl uenza pandemics are caused by infl uenza viruses from nonhuman reservoirs: among the infl uenza pandemics [14] and the other two, in 1957 and 1968, were caused by new strains resulting from the combination of avian and human viruses through a reassortment process [15, 16] . Viral infl uenza A is a pandemic caused by a novel infl uenza virus A/H1N1, which spread worldwide from Mexico in March 2009. The infection is due to pigto-human transmission of a viral pathogen produced by the triple genetic reassortment of human, swine and avian viral strains in North America and Eurasia; human-to-human transmission occurs through respiratory droplets or contact with infected surfaces [9, 14, 16] .

According to the WHO, from the beginning of the pandemic to 15 November 2009, >78,000 cases of infl uenza A H1N1 were notifi ed in Europe and 190,765 in the Americas, with a death toll of at least 350 and 4,806, respectively [17] . From 19 October, when Infl unet monitoring began in Italy [18] , to 8 November, there were an estimated 1,521,000 cases of infl uenza A/H1N1 in Italy [19] . In un recente lavoro [8] è stato confermato che il virus H1N1 si trasmette caratteristicamente tra bambini e giovani adulti, colpendo nel 45% dei casi giovani di età <18 anni e solo nel 5% dei casi individui di età >65 anni. Sebbene nella nostra personale esperienza la gravità dell'impatto epidemiologico dell'infl uenza H1N1 sia stato ampiamente ridimensionato rispetto alle aspettative globali, anche la nostra popolazione di studio ha presentato un prevalente interessamento delle fasce di età più giovanili and 53 deaths according to the ECDC (European Centre for Disease Prevention and Control (ECDC) [19] . The Italian regions that recorded the highest incidence of the virus were: Marche (2.9%), followed by Emilia Romagna (1.8%), Latium (1.7%), Abruzzo (1.6%) and Campania (1.6%). As of 15 November 2009, when the infection reached its peak, Fig. 3a,b A 63 year-old man with obesity and COPD treated with oxygen therapy. Clinical fi ndings: high fever and acute respiratory failure. a Chest X-ray, posteroanterior projection: CONS, preferentially distributed in the lower and middle lung fi elds. b Axial chest MDCT: bilateral pulmonary CONS associated with diffuse GGO are preferentially distributed peripherally and posteriorly and in the apices of the lower lobes. [8, 19] : il 68,7% era <18 anni, il 3,5% degli individui era di età >65 anni. È stato ipotizzato che gli individui anziani siano dotati di anticorpi neutralizzanti cross-reattivi verso il virus H1N1 [20] . La più alta incidenza nelle fasce di età inferiori ai 18 anni potrebbe essere legata, invece, in particolar modo nei bambini, a meccanismi di immunodefi cienza e/o di immaturità immunologica [21, 22] .

Le principali manifestazioni cliniche dell'infl uenza virale H1N1 descritte in letteratura [8] sono rappresentate da: febbre (95%), tosse (88%), cefalea (34%), faringodinia (31%), vomito (29%), diarrea (25%). In accordo con tali dati, i segni clinici di infl uenza A identifi cati nel nostro gruppo di studio sono stati febbre (96,4%), tosse (85,6%), angina (41,3%), vomito (34,1%) e diarrea (41,3%). In accordo con i dati della letteratura [8] abbiamo osservato un elevazione degli indici di funzionalità epatica (44,9%), dei leucociti (17,9%) e trombocitopenia (2,9%) . Le principali patologie concomitanti sono state bronchite asmatica the number of infl uenza A victims had risen to 53, 23 of whom were in Campania, seven in Emilia Romagna, and fi ve in Lombardy. All but three were affected by severe underlying conditions. The most affected age groups were children and teenagers from birth to 14 years of age (incidence 3.6%), and, to a lesser extent, individuals aged 15-64 years (0.7%) and >65 years (0.1 %) [19] . A recent paper [8] confi rmed that the H1N1 virus is typically transmitted among children and young adults, affecting individuals <18 years in 45% of cases and those >65 years in 5% of cases only. Although in our personal experience the epidemiological impact of H1N1 infl uenza has been substantially milder than expected, our study population showed a prevalent involvement of the younger age groups [8, 19] : 68.7% <18 years of age, 3.5% >65 years. It has been suggested that older individuals have cross-reactive neutralising antibodies to the H1N1 virus [20] . The higher incidence among individuals <18 years of age may, instead, be related -espe- (45,5%), con valori percentuali più alti rispetto ai dati della letteratura [8] , cardiopatie (38,9%) e diabete (14,9%) . Allo stato attuale sono stati realizzati pochi studi di imaging del torace nei pazienti affetti da infl uenza virale A/ H1N1 [10] [11] [12] . La presentazione della polmonite virale H1N1, sia alla radiografi a del torace che alla TC sembra rispecchiare le caratteristiche generali delle polmoniti virali [23] . Alcuni autori [11] hanno descritto le principali alterazioni radiografi che e TC in 7 pazienti affetti da infl uenza A/H1N1: opacità ground-glass bilaterali, più di frequente associate ad aree di consolidamento a distribuzione multifocale, talora anche focali. All'indagine TC le opacità ground-glass e le aree di consolidamento presentavano una predominante distribuzione peribroncovascolare e subpleurica. Agarwal et al. [10] In accordo con i dati della letteratura [10, 11] , le principali lesioni elementari da noi individuate alla Rx del torace (53%) (Tabella 1) sono state CM (55,5%), ad estensione prevalentemente bilaterale, simmetrica, diffusa/multifocale (14%/14%) ed a distribuzione predominante basale (46%) (Figg. 2a, 3a ) ma anche OGG (14,4%) (Fig. 1a) . Queste ultime presentavano, tuttavia, un'estensione prevalentemente monolaterale e focale (61,5%) e distribuzione più evidente in sede medio-basale (46,1%). Meno rappresentativa (6,6%) è stata, nella nostra casistica, l'associazione di CM e OGG che mostravano estensione diffusa, simmetrica e multifocale (83,3%) e predominante distribuzione medio-basale (50%) (Fig. 4a) . Alla Rx del torace abbiamo registrato, caratteristicamente, un'elevata percentuale di pazienti con RI (58,8%) (Fig. 1a) 17/20 (85%) pazienti reperti patologici. In accordo con i dati della letteratura [10, 11] le lesioni elementari evidenziate in TC (Tabella 2) sono state OGG associate a CM (58,8%), ambedue ad estensione bilaterale, cially as regards children -to mechanisms of immunodeficiency and/or immunological immaturity [21, 22] .

The most important reported [8] clinical manifestations of H1N1 virus infl uenza are: fever (95%), cough (88%), headache (34%), sore throat (31%), vomiting (29%) and diarrhoea (25%). In agreement with these data, the clinical signs of infl uenza A identifi ed in our study population were fever (96.4%), cough (85.6%), angina (41.3%), vomiting (34.1%) and diarrhoea (41.3%). In addition, similar to previous reports [8] , we found elevated liver function tests (44.9%), leucocytes (17.9%) and thrombocytopenia (2.9%). The main underlying conditions were asthmatic bronchitis (45.5%), which was more frequent than reported in the literature [8] , heart disease (38.9%) and diabetes (14.9%).

To date, few studies addressing chest imaging in patients affected by infl uenza A/H1N1 have been published [10] [11] [12] , and the presentation of H1N1 virus pneumonia on both CXR and chest CT seems to refl ect the general features of viral pneumonia [23] . One study [11] reported on the main CXR and chest CT fi ndings in seven patients affected by infl uenza A/H1N1: bilateral GGO, more frequently associated with focal or multifocal areas of consolidation. At CT, the GGO and the areas of consolidation had a predominant peribronchovascular and subpleural distribution. Agarwal et al. [10] conducted a larger study involving 222 patients with infl uenza A/H1N1 seen between May and July 2009. Of the 66 (30%) patients studied with CXR, 28 (42%) had consolidations (50%), more frequently distributed in the lower lobes. Of the 15/66 (22.7%) patients who underwent CT, 9/15 (60%) had GGO combined with consolidation, with diffuse or lobar extension in 70% of cases. Thromboembolic complications occurred in 8% of cases, and 8% of the patients died.

In agreement with the literature [10, 11] , the main primary pulmonary lesions we identifi ed on CXR (53%) ( Table 1) were consolidations (55.5%), with prevalent bilateral, symmetrical, diffuse/multifocal extension (14%/14%) and predominant basal distribution (46%) (Figs. 2a, 3a) , and GGO (14.4%) (Fig. 1a) . The latter had, however, prevalent unilateral and focal extension (61.5%) and predominant distribution in the middle-basal region (46.1%). In our series, we had fewer cases (6.6 %) of consolidation combined with GGO, which showed diffuse, symmetrical and multifocal extension (83.3%) and predominant middlebasal distribution (50%) (Fig. 4a) . At CXR we found a typically high proportion of patients with interstitial reticulation (58.8%) (Fig. 1a) , which showed bilateral, symmetrical and diffuse extension (90.6%) and predominant basal distribution (86.8%). It is likely that the alarmism regarding infl uenza infection prompted many patients to seek early medical attention, thus allowing detection of interstitial reticulation, an early fi nding in viral disease. Only 5% of patients had con una maggiore tendenza alla distribuzione asimmetrica e multifocale (80%) (Fig. 2b) , piuttosto che diffusa e simmetrica (20%) (Fig. 4b,c) . La distribuzione delle OGG associate ai CM è stata predominante ai lobi inferiori (60%) ed in sede subpleurica, associata nel 60% dei casi ad omologhe lesioni in sede peribroncovascolare. Inoltre non sono stati evidenziati CM isolati in assenza di OGG verosimilmente per la relativa precocità di osservazione delle lesioni elementari polmonari: nella fase iniziale di infezione le OGG, lesioni più precoci in cui sono ancora distinguibili bronchi e vasi, si manifestano insieme ai CM, rispetto a fasi più tardive della patologia, non necessariamente evolventi in ARDS, in cui esse aumentano la loro densitometria e confl uiscono interamente in consolidamenti. All'indagine TC sono stati identifi cati, inoltre, 82,3% casi di RI, a prevalente estensione bilaterale, diffusa e simmetrica (78,6%) con predominante distribuzione medio-basale (Fig. 1b) [10] , negli esami eseguiti con mezzo di contrasto endovena per quesito clinico di embolia polmonare, non abbiamo evidenziato fenomeni di natura tromboembolica a carico delle arterie polmonari e dei suoi rami.

La letteratura moderna [24] [25] [26] ha ampiamente descritto le principali alterazioni polmonari identifi cabili in caso di infezione batterica: consolidazioni con broncogramma aereo, tree-in-bud, cavitazioni,versamento pleurico e/o pericardico, linfoadenomegalie. In accordo con i dati della letteratura [24] [25] [26] , sebbene differentemente identifi cati nelle due metodiche di studio (Tabelle 1 e 2), i segni di sovrainfezione batterica più frequenti nel nostro gruppo di studio sono stati tree-in-bud, CM con broncogramma aereo, versamento pleurico e pericardico. All'esame colturale e nel bronco aspirato, in 3/9 casi (33,3%) è stato identifi cato il batterio S. aureus, in 6/9 casi (66,7%) una fl ora batterica mista. Dei Figg. 3 e 4) .

Il nostro studio ha permesso di determinare le principali nodules, which showed unilateral and focal extension and basal distribution in 60% of cases.

Of 20/167 (11.9%) patients studied with CT, 17/20 (85%) showed pathological abnormalities. In agreement with the literature [10, 11] the primary lesions identifi ed on CT (Table 2) were GGO combined with consolidation (58.8%), both with bilateral extension and a tendency to asymmetrical and multifocal (80%) (Fig. 2b) , rather than diffuse and symmetrical distribution (Fig. 4b,c) (20%). The distribution of GGO combined with consolidation was predominant in the lower lobes (60%) and subpleural regions and was associated in 60% of cases with similar peribronchovascular lesions. Additionally, there were no cases of isolated consolidation without GGO, probably owing to the relatively early observation of the primary pulmonary lesions: in the initial phase of infection, GGOs -earlier lesions in which bronchial and vessel margins are still discernible -manifest alongside consolidations compared with the later phases of disease (not necessarily evolving to ARDS) in which they increase in attenuation and coalesce into consolidations. On CT we also identifi ed 82.3% cases of interstitial reticulation, with prevalent bilateral, diffuse and symmetrical extension (78.6%) and predominant middle-basal distribution (Fig. 1b) . These fi ndings appear to corroborate the CXR results and refl ect, similarly to CXR, the same early observation of the radiographic fi ndings. Only two cases showed parenchymal nodules, which were focal and unilateral and distributed in the lower lobe; these nodules had already been identifi ed at CXR and were referable to an underlying infectious disease. At variance with previous reports [10] , in the contrast-enhanced examinations requested for suspected pulmonary embolism, we found no thromboembolic phenomena involving the pulmonary arteries or their branches.

Recent literature [24] [25] [26] has extensively described the principal pulmonary abnormalities seen in bacterial infections: consolidations with air bronchogram, tree-in-bud pattern, cavitation, pleural and/or pericardial effusion and lymphadenopathy. In agreement with these data [24] [25] [26] , although differently identifi ed by the two imaging modalities (Tables 1 and 2) , the most common signs of bacterial suprainfection in our series were tree-in-bud pattern, consolidation with air bronchogram and pleural and pericardial effusion. Blood and bronchoaspirate culture revealed S. aureus in 3/9 cases (33.3%) and mixed bacterial fl ora in 6/9 cases (66.7%). Of the 15/167 patients (8.98%) who received mechanical ventilation due to worsening clinical and radiological features, all had an underlying condition, and in particular, COPD (33.3%). Six of these 15 patients died (40%): four (66.6%) due to ARDS. In agreement with the literature [27] , the radiographic and CT fi ndings in these 15 patients were characterised by diffuse and bilateral GGO and consolidation (Figs. 3, 4) .

caratteristiche radiologiche e cliniche di un'ampia popolazione di pazienti ospedalizzati in un centro di riferimento per le malattie infettive con diagnosi accertata, mediante tampone faringeo, di infl uenza virale H1N1. L'ampia casistica radiologica e l'integrazione, quando necessaria, con esame TC hanno consentito di determinare le principali alterazioni polmonari dell' infl uenza virale H1N1. L'esame radiografi co standard e la tomografi a computerizzata del torace hanno rappresentato le indagini di riferimento nell'individuazione della sede ed estensione delle lesioni elementari polmonari, documentando i segni di sovrainfezione batterica e le complicanze polmonari dell'infl uenza H1N1, ai fi ni di un corretto inquadramento diagnostico, prognostico e terapeutico.

Our study allowed us to determine the main clinical features of a large population of patients admitted to an infectious disease referral centre with a diagnosis of H1N1 virus infl uenza proved by pharyngeal swab. The large patient sample, and supplementation when needed with CT, allowed us to defi ne the main pulmonary abnormalities seen in H1N1 virus infl uenza. Standard CXR and chest CT are the reference investigations in identifying the location and extension of primary pulmonary lesions and documenting the signs of bacterial suprainfection and pulmonary complications of H1N1 infl uenza, thus allowing correct diagnostic, prognostic and therapeutic management.

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Characterization of the 1918 infl uenza virus polymerase genes

Genetic analysis of human H2N2 and early H3N2 infl uenza viruses, 1957-1972: evidence for genetic divergence and multiple reassortment events

Triple-reassortant swine infl uenza A (H1) in humans in the United States

Pandemia da infl uenza umana da virus A/H1N1v-Aggiornamento 75

Ministero del Lavoro, della Salute e delle politiche sociali, Infl uenza A/H1N1, Il punto della situazione al 15 novembre

Cross-reactive antibody responses to the 2009 pandemic H1N1 infl uenza virus

Immunocompetence of children with frequent respiratory infection

Pediatric hospitalizations associated with 2009 pandemic infl uenza A (H1N1) in Argentina

Viral pneumonias in adults: radiologic and pathologic fi ndings

Radiology of bacterial pneumonia

Imaging of pneumonia: trends and algorithms

Imaging fi ndings in a fatal case of pandemic swine-origin infl uenza A (H1N1)